title: Upregulation of lipid synthesis in small rat adipocytes by microvesicle-associated CD73 from large adipocytes.
abstract: Filling-up lipid stores is critical for size increase of mammalian adipocytes. The glycosylphosphatidylinositol (GPI)-anchored protein, CD73, is released from adipocytes into microvesicles in response to the lipogenic stimuli, palmitate, the antidiabetic sulfonylurea drug glimepiride, phosphoinositolglycans (PIG), and H(2)O(2). Upon incubation of microvesicles with adipocytes, CD73 is translocated to cytoplasmic lipid droplets (LD) and esterification is upregulated. The role of CD73-harboring microvesicles in coordinating esterification between differently sized adipocytes was studied here. Populations consisting of either small or large or of both small and large isolated rat adipocytes as well as native adipose tissue pieces from young and old rats were incubated with or depleted of endogenous microvesicles and analyzed for translocation of CD73 and esterification in response to the lipogenic stimuli. Large adipocytes exhibited higher and lower efficacy in releasing CD73 into microvesicles and in translocating CD73 to LD, respectively, compared to small adipocytes. Populations consisting of both small and large adipocytes were more active in esterification in response to the lipogenic stimuli than either small or large adipocytes. With both adipocytes and adipose tissue pieces from young rats esterification stimulation by the lipogenic stimuli was abrogated by depletion of CD73-harboring microvesicles from the incubation medium and interstitial spaces, respectively. In conclusion, stimulus-induced lipid synthesis between differently sized adipocytes is controlled by the release of microvesicle-associated CD73 from large cells and its subsequent translocation to LD of small cells. This information transfer via microvesicles harboring GPI-anchored proteins may shift the burden of triacylglycerol storage from large to small adipocytes.
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Research & Development, Diabetes Division, Frankfurt am Main, Germany. guenter.mueller@sanofi-aventis.com
authors.forename: Günter
authors.initials: G
authors.lastname: Müller
authors.forename: Marion
authors.initials: M
authors.lastname: Schneider
authors.forename: Gabriele
authors.initials: G
authors.lastname: Biemer-Daub
authors.forename: Susanne
authors.initials: S
authors.lastname: Wied
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D004951:Esterification; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism / Q000502:physiology*; D050155:Lipogenesis; D008297:Male; D019308:Palmitic Acid / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D022161:Transport Vesicles; D015854:Up-Regulation
chemical_list: D017261:Glycosylphosphatidylinositols; D013453:Sulfonylurea Compounds; D019308:Palmitic Acid; C057619:glimepiride; D006861:Hydrogen Peroxide